A new synthesis of 2,3-disubstituted quinoxaline 1,4-dioxides catalyzed by molecular sieves

The syntheses of 2,3-disubstituted quinoxaline 1,4-dioxides are smoothly and efficiently carried out by the adsorption of the components on molecular sieve 3A (powder) from benzofuroxan 1 and 1,3-diketones, 3-oxo-alkanoic esters, or 3-oxoalkanamides 2 .     

Regioselective synthesis of 1,4-disubstituted imidazoles

A short and efficient synthesis of 1,4-disubstituted imidazoles has been developed which provides the desired products with complete regioselectivity. This protocol allows preparation of compounds which are challenging to prepare by current literature methods in a regioselective fashion, a sterically and electronically diverse range of N-substituents being accessible. The sequence involves an unusual double aminomethylenation of a glycine derivative, to yield a 2-azabuta-1,3-diene, onto which addition of an amine nucleophile results in a transamination/cyclization to prepare the substituted imidazole. The cyclization event is surprisingly insensitive to steric and electronic variations on the amine component, enabling a diverse range of imidazoles to be prepared.     

One-pot synthesis of enantiomerically enriched 2,3-disubstituted cyclopentanones via copper-catalyzed 1,4-reduction and alkylation

[reaction: see text]. Enantiomerically enriched 2,3-disubstituted cyclopentanones were prepared via copper-catalyzed 1,4-reduction of 3-substituted cyclopentenones followed by alkylation of the resulting silyl enol ether. Using this procedure, trans-2,3-disubstituted cyclopentanones were produced in moderate to good overall yields (42-67%) and with excellent enantiomeric and diastereomeric excesses. The reduction and alkylation were performed in a single reaction vessel.     

Stereospecific synthesis of azetidine-cis-2,3-dicarboxylic acid

Electrocyclic reaction product of 1-(methoxycarbonyl)-1,2-dihydropyridine was stereospecifically converted by RuO(4) oxidation into azetidine-cis-2,3-dicarboxylic acid.     

Head-to-head polymers. XV. A facile synthesis of 2,3-disubstituted succinates and butanediols-1,4

A synthetic approach that makes symmetrically 2,3-dialkyl-substituted succinates and compounds prepared from 2,3-dialkyl-substituted succinates easily available has been developed. Coupling of α-bromoalkanoic esters with a zinc/copper couple produced in about 40% yield 2,3-disubstituted succinates which were reduced with LiAlH₄ to 2,3-disubstituted butanediols-1,4 in nearly quantitative yields. Some 2,3-disubstituted butanediols-1,4 were cyclodehydrated under reduced pressure with KHSO₄ to 3,4-disubstituted tetrahydrofurans or acetylated and the diacetyl compounds pyrolyzed at 525°C to 2,3 disubstituted butadienes-1,3. The length of the alkyl chains of the 2,3-dialkylsuccinates and consequently the 2,3-dialkylbutanediols-1,4 ranged from C₂ to C₁₆. 2,3-Disubstituted butanediols-1,4, 2,3-disubstituted butadienes-1,3, and 3,4-disubstituted tetrahydrofurans are interesting monomers for polymerization experiments.     

A new synthesis of 2,3-disubstituted indoles

A novel synthesis of 2,3-disubstituted indoles starting from N-alkyl-N-propvnyl anilines is described. The reactions employed are analogous to the thermal rearrangement of aryl propynyl sulfoxides.     

A convenient synthesis of 1,4-disubstituted imidazoles

An efficient method for the regioselective protection of 4-alkyl-, 4-iodo, 4-vinylimidazoles has been developed via an alkylation-isomerization sequence with various imidazole-protecting groups. The initially formed mixture of 4/5-alkyl-, 4/5-iodo, and 4/5-vinylimidazoles are isomerized to the corresponding 4-isomers on treatment of a DMF solution with a small amount of RX and heating at 75 °C.     

Stereoselective synthesis of 1,4-disubstituted 1,3-diene

New synthetic methods for the preparation of 1,3-dienes are described.     

Stereocontrolled chemoenzymatic synthesis of 2,3-disubstituted piperidines

(R,R)-2,3-Disubstituted piperidines were readily synthesized starting from (R)-(+)-5-bromo-2-hydroxypentanenitrile (R)-2. An enantioselective (R)-oxynitrilase-catalyzed transcyanation was used to prepare the starting cyanohydrin (R)-2.     

Asymmetric synthesis of trans-2,3-disubstituted indoline derivatives

A novel method for asymmetric synthesis of trans-2,3-disubstituted indolines has been developed. The strategy involves the (-)-sparteine-mediated electrophilic substitution of 2-benzyl N-pivaloylaniline with aromatic or α,β-unsaturated aldehydes and subsequent intramolecular nucleophilic substitution. The simple protocol for two-step process can produce highly enantioenriched indolines 3a-o up to 98:2 er.     

Asymmetric synthesis of 4,4-disubstituted alka-2,3-dienoates

The Horner-Emmons reaction of P-chiral carbanion 1 derived from the optically active 2 with a series of unsymmetrical ketenes leading to the title aliene esters 4 is described. When (S)?( ? )?2 was used as a starting material, the enantiomerically enriched (R)( ? )?4a as well as 4b were obtained. On the basis of these results the stereochemical course of the Horner-Enunons reaction is discussed and configurations of the other aliene esters obtained are proposed.     

One-pot synthesis of 1,4-disubstituted 1,2,3-triazoles from nitrobenzenes

A facile synthesis of 1,4-disubstituted 1,2,3-triazoles was achieved from nitrobenzenes and terminal alkynes under mild conditions. The reactions were successful for nitrobenzenes and terminal alkynes bearing various functionalities, from which the 1,2,3-triazole derivatives were smoothly synthesized through a four-step one-pot sequence.     

Sequential cross-coupling of 1,4-bissilylbutadienes: synthesis of unsymmetrical 1,4-disubstituted 1,3-butadienes

A mild and general and stereospecific cross-coupling reaction of unsymmetrical 1,4-bissilyl-1,3-butadienes has been accomplished. By the use of either a benzyldimethylsilyl or 2-thienyldimethylsilyl unit at one end of the dienylsilanol, a selective cross-coupling could be effected under mildly basic conditions (KOTMS) to afford 4-aryl-1,3-dienylsilanes in excellent yield for a wide range of aryl and alkenyl coupling partners. The second cross-coupling could be effected cleanly by the action of TBAF with electron-rich or electron-poor halides. The sequential process could be telescoped into a "one pot" procedure with overall excellent yields of the unsymmetrical 1,4-diaryl-1,3-butadienes.     

Stereospecific synthesis and carbon-13 nmr spectra of 1,4-epoxydecahydronaphthalenes

The stereoselective synthesis of cis-fused 1,4-epoxydecahydronaphthalenes from transannular reactions of medium-ring compounds is described. The carbon-13 nmr spectra of both are reported, and assignments of the various resonances have been made based on model compounds and off-resonance decoupling experiments.     

Silica gel promoted environment-friendly synthesis of 2,3-disubstituted 4-thiazolidinones

Three-component one pot silica gel promoted synthesis of 2,3-disubstituted 4-thiazolidinones is described. The method provides rapid and easy access to thiazolidinone compounds in good to excellent yields.     

Direct synthesis of 4,4-disubstituted N-silyl-1,4-dihydropyridines

An unprecedented method for the preparation of 4,4-disubstituted 1,4-dihydropyridines is presented. It is based on the trapping reaction of 4-substitued N-silylpyridinium ions. When performed with dialkylmagnesium reagents, such as iPr₂Mg, silyl protected 4,4-disubstituted 1,4-dihydropyridines were obtained in up to quantitative yields. High 1,4-selectivity was found for sterically demanding nucleophiles, whereas small nucleophiles (Me₂Mg) tend to yield 1,2-addition-products. Grignard, dialkylzinc and organocopper reagents were found to give either no addition products or less favorable results. Reduction of the obtained 1,4-dihydropyridine with NaCNBH₃ in the presence of HCl, followed by treatment with tert-butyl dicarbonate provided the corresponding N-Boc protected piperidines with high yields.     

A new entry to the synthesis of 2,3-disubstituted indoles

[reaction: see text] The Stille coupling of N-acyl-2-iodoanilines with the 1-(tributylstannyl)-1-substituted allenes affected the successive one-step formation of the 2-methyl-3-substituted indoles. Alternatively, the other type of 2-alkyl-3-substituted indoles could be synthesized in a one-pot operation, which consists of the Stille coupling reaction with the 1-(tributylstannyl)-1,3-disubstituted allenes, followed by TBAF treatment. This procedure could be applied to the synthesis of indomethacin.     

Stereospecific substitution of a hydroxy group by a chlorine atom in isomeric 2,3-disubstituted 3-hydroxytetrahydrothiophenes

The stereospecific synthesis of the three possible isomers of 4-amino-3-chloro-2-(4-methoxycarbonylbutyl)tetrahydrothiophene hydrohalides from the corresponding isomers of 4-amino-3-hydroxytetrahydrothiophene by the action of thionyl chloride was realized. Three isomers of 4-ureido-3-chloro-2-(4-methoxycarbonylbutyl)tetrahydrothiophene were obtained from the 3-chlorotetrahydrothiophene derivatives. The configurations of the isomeric compounds obtained were proved by ¹H and ¹³C NMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 327–333, March, 1991.     

A facile synthesis of 2,3-disubstituted furo[2,3-b]pyridines

In a three-step sequence starting from readily available starting materials, 2,3-carbon disubstituted furo[2,3-b]pyridines can be accessed in good yields and purity. Furo[2,3-b]pyridines bearing ester, amide and ketone groups at the 2-position can be prepared with a variety of aryl and alkyl groups at the 3-position.